Comparison of the King's and MiToS staging systems for ALS

Abstract

Objective: To investigate and compare two ALS staging systems, King's clinical staging and Milano-Torino (MiToS) functional staging, using data from the LiCALS phase III clinical trial (EudraCT 2008-006891-31).

Methods: Disease stage was derived retrospectively for each system from the ALS Functional Rating Scale-Revised subscores using standard methods. The two staging methods were then compared for timing of stages using box plots, correspondence using chi-square tests, agreement using a linearly weighted kappa coefficient and concordance using Spearman's rank correlation.

Results: For both systems, progressively higher stages occurred at progressively later proportions of the disease course, but the distribution differed between the two methods. King's stage 3 corresponded to MiToS stage 1 most frequently, with earlier King's stages 1 and 2 largely corresponding to MiToS stage 0 or 1. The Spearman correlation was 0.54. There was fair agreement between the two systems with kappa coefficient of 0.21.

Conclusion: The distribution of timings shows that the two systems are complementary, with King's staging showing greatest resolution in early to mid-disease corresponding to clinical or disease burden, and MiToS staging having higher resolution for late disease, corresponding to functional involvement. We therefore propose using both staging systems when describing ALS.

Keywords: Clinical stage; King’s stage; MiToS stage; clinical trials; prognosis.

Figure 1.

Flowchart of ALS staging systems and their definitions (King’s staging and MiToS staging).

Figure 2.

Box plot for Standardised Median Time (SMT) from onset to each disease stage. (A) SMT for King’s stages. (B) SMT for MiToS stages. The y-axis represents the proportion of disease time elapsed, where 0 is disease onset and 1 is death. Horizontal lines on each plot represent the following: minimum, lower quartile, median, upper quartile and maximum values, read from bottom to top. Mean values are marked by ‘x’ and outliers by ‘•’.

Figure 3.

Three-dimensional bar chart showing the count of patients in each clinical stage by both systems. The y-axis represents the number of patients, x-axis the MiToS stage (0-4) and z-axis the King’s stage (1–4) of disease progression.